PROJECT SUMMARY/ABSTRACT Because obesity has reached epidemic proportions, there is escalating interest in bariatric surgery, including Roux-en-Y gastric bypass. Gastric bypass surgery is highly effective for the treatment of obesity and related comorbidities, but it has negative effects on skeletal health, with large increases in bone turnover, substantial decreases in bone mineral density, and increased fracture incidence. Postmenopausal women appear particularly at risk. The decline in skeletal integrity is fueled in part by a dramatic decline in intestinal calcium absorption capacity, independent of vitamin D status. The very high calcium intake that would be necessary to overcome the reduced absorption may be burdensome and ineffective, so an intervention to improve calcium bioavailability is needed. Animal and human research suggests that non-digestible fibers termed prebiotics, such as soluble corn fiber (SCF), augment calcium absorption in the lower intestine, the segment of the gut remaining intact after gastric bypass, as they act as substrates for beneficial gut microbiota. However, effects of prebiotics on calcium absorption have not been examined in the gastric bypass population. Our objective is to identify a strategy to enhance calcium absorption after gastric bypass surgery, and in consequence, to prevent detrimental nutritional effects on bone metabolism and to attenuate negative skeletal consequences of the operation. We hypothesize that a prebiotic is such a strategy. To test this hypothesis, we will perform a pilot randomized controlled trial (RCT) of the effects of SCF in 20 postmenopausal women who underwent gastric bypass surgery 2-6 years previously and thus have completed the postoperative period of rapid weight loss. Participants will be randomized to a 2-month course of 20 g/day SCF vs. maltodextrin placebo in a calorie-free beverage. First, we will test the hypothesis that SCF increases intestinal calcium absorption and decreases bone turnover marker levels in those who have undergone gastric bypass (Aim 1). We will measure fractional calcium absorption using a gold-standard dual stable isotope method. Next, we will determine the tolerability and acceptability of SCF in those who have undergone gastric bypass (Aim 2). Using a short daily questionnaire, we will monitor adherence and assess for the presence and severity of gastrointestinal symptoms including flatulence, bloating, and abdominal pain. Finally, we will examine whether changes in the gut microbiome mediate SCF effects on calcium absorption (Aim 3). To explore potential mechanisms for the effects of SCF, we will perform 16S rRNA profiling and bacterial metagenomic predictions on fecal specimens before and after SCF vs. placebo. This pilot trial will inform a larger and longer-term RCT with these as well as skeletal outcomes (i.e., bone mass and structure). Ultimately, if SCF augments calcium absorption capacity and improves bone health, it could become part of an evidence-based postoperative nutrition program. This contribution will be significant in shaping the direct care of gastric bypass patients, informing the prevention of potential skeletal complications of an otherwise beneficial surgical procedure.